Title | Type I IFN promotes NK cell expansion during viral infection by protecting NK cells against fratricide. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Madera S, Rapp M, Firth MA, Beilke JN, Lanier LL, Sun JC |
Journal | J Exp Med |
Volume | 213 |
Issue | 2 |
Pagination | 225-33 |
Date Published | 2016 Feb 08 |
ISSN | 1540-9538 |
Keywords | Animals, Apoptosis, Cell Proliferation, Herpesviridae Infections, Interferon Type I, Killer Cells, Natural, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Mice, Knockout, Muromegalovirus, NK Cell Lectin-Like Receptor Subfamily K, Perforin, Receptor, Interferon alpha-beta, STAT1 Transcription Factor |
Abstract | Type I interferon (IFN) is crucial in host antiviral defense. Previous studies have described the pleiotropic role of type I IFNs on innate and adaptive immune cells during viral infection. Here, we demonstrate that natural killer (NK) cells from mice lacking the type I IFN-α receptor (Ifnar(-/-)) or STAT1 (which signals downstream of IFNAR) are defective in expansion and memory cell formation after mouse cytomegalovirus (MCMV) infection. Despite comparable proliferation, Ifnar(-/-) NK cells showed diminished protection against MCMV infection and exhibited more apoptosis compared with wild-type NK cells. Furthermore, we show that Ifnar(-/-) NK cells express increased levels of NK group 2 member D (NKG2D) ligands during viral infection and are susceptible to NK cell-mediated fratricide in a perforin- and NKG2D-dependent manner. Adoptive transfer of Ifnar(-/-) NK cells into NK cell-deficient mice reverses the defect in survival and expansion. Our study reveals a novel type I IFN-dependent mechanism by which NK cells evade mechanisms of cell death after viral infection. |
DOI | 10.1084/jem.20150712 |
Alternate Journal | J. Exp. Med. |
PubMed ID | 26755706 |
PubMed Central ID | PMC4749923 |
Grant List | R01 AI100874 / AI / NIAID NIH HHS / United States AI068129 / AI / NIAID NIH HHS / United States P30 DK026743 / DK / NIDDK NIH HHS / United States AI085034 / AI / NIAID NIH HHS / United States T32GM07739 / GM / NIGMS NIH HHS / United States T32 AI007621 / AI / NIAID NIH HHS / United States P30 CA008748 / CA / NCI NIH HHS / United States T32AI007621 / AI / NIAID NIH HHS / United States P30CA008748 / CA / NCI NIH HHS / United States R01 AI068129 / AI / NIAID NIH HHS / United States R00 AI085034 / AI / NIAID NIH HHS / United States T32 GM007739 / GM / NIGMS NIH HHS / United States AI100874 / AI / NIAID NIH HHS / United States |
Submitted by kej2006 on June 6, 2018 - 4:11pm